AIMP1

aminoacyl tRNA synthetase complex interacting multifunctional protein 1, the group of Aminoacyl tRNA synthetase complex interacting multifunctional proteins

Basic information

Region (hg38): 4:106315544-106349456

Previous symbols: [ "SCYE1" ]

Links

ENSG00000164022 ∙ NCBI:9255 ∙ OMIM:603605 ∙ HGNC:10648 ∙ Uniprot:Q12904 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hypomyelinating leukodystrophy 3 (Strong), mode of inheritance: AR
• hypomyelinating leukodystrophy 3 (Moderate), mode of inheritance: AR
• autosomal recessive non-syndromic intellectual disability (Supportive), mode of inheritance: AR
• hypomyelinating leukodystrophy 3 (Supportive), mode of inheritance: AR
• hypomyelinating leukodystrophy 3 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Leukodystrophy, hypomyelinating, 3	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	21092922; 21397066; 21397067; 24958424

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the AIMP1 gene.

• not provided (9 variants)
• Hypomyelinating leukodystrophy 3 (3 variants)
• Hypotonia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the AIMP1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				10	2	12
missense			44	3	2	49
nonsense	3	1				4
start loss			1	1		2
frameshift	6	1	1			8
inframe indel			3			3
splice donor/acceptor (+/-2bp)		1	1			2
splice region			1		1	2
non coding	1		4	5	9	19
Total	10	3	54	19	13

Highest pathogenic variant AF is 0.0000657

Variants in AIMP1

This is a list of pathogenic ClinVar variants found in the AIMP1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
4-106316238-C-T			Benign (Nov 10, 2018)
4-106316331-C-T			Benign (Jun 19, 2021)
4-106316548-A-G		not specified	Uncertain significance (Mar 13, 2023)
4-106316550-G-C			Uncertain significance (Feb 01, 2018)
4-106316586-C-T		AIMP1-related disorder	Likely benign (Aug 09, 2019)
4-106316858-A-G			Benign (Jun 18, 2021)
4-106324979-C-A		not specified	Benign (Jul 15, 2024)
4-106325015-AAAT-A		Hypomyelinating leukodystrophy 3	Uncertain significance (Dec 02, 2021)
4-106325019-A-G		Inborn genetic diseases	Uncertain significance (Feb 16, 2023)
4-106325033-G-C			Benign (Jan 29, 2024)
4-106325050-A-G		Inborn genetic diseases	Uncertain significance (Oct 13, 2023)
4-106325076-G-C			Uncertain significance (Aug 31, 2022)
4-106325078-A-C			Uncertain significance (Mar 01, 2022)
4-106325080-A-T		Inborn genetic diseases	Uncertain significance (Aug 01, 2022)
4-106325086-AG-A			Pathogenic (Aug 10, 2022)
4-106325091-C-T		Hypotonia	Pathogenic (-)
4-106325096-TTCTC-T			Pathogenic (Jul 21, 2022)
4-106325101-T-C		Inborn genetic diseases	Uncertain significance (May 26, 2024)
4-106325105-T-C			Likely benign (Sep 27, 2022)
4-106327456-C-T		Hypomyelinating leukodystrophy 3 • AIMP1-related disorder	Pathogenic/Likely pathogenic (Jan 26, 2023)
4-106327462-A-G		Inborn genetic diseases	Uncertain significance (Sep 20, 2023)
4-106327466-T-C			Uncertain significance (Jul 27, 2022)
4-106327486-C-T			Pathogenic (Feb 24, 2023)
4-106327487-G-A		Inborn genetic diseases	Uncertain significance (Feb 13, 2024)
4-106327500-TA-T		Hypomyelinating leukodystrophy 3	Pathogenic (Oct 25, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
AIMP1	protein_coding	protein_coding	ENST00000394701	7	33683

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.04e-7	0.541	125708	0	37	125745	0.000147

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.207	182	174	1.04	0.00000855	2198
Missense in Polyphen		45	61.779	0.7284		852
Synonymous	0.500	55	59.9	0.918	0.00000311	645
Loss of Function	0.923	12	16.0	0.751	8.07e-7	200

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000116	0.000116
Ashkenazi Jewish	0.000199	0.000198
East Asian	0.000109	0.000109
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.000159	0.000158
Middle Eastern	0.000109	0.000109
South Asian	0.000229	0.000229
Other	0.000327	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Non-catalytic component of the multisynthase complex. Stimulates the catalytic activity of cytoplasmic arginyl-tRNA synthase (PubMed:10358004). Binds tRNA. Possesses inflammatory cytokine activity (PubMed:11306575). Negatively regulates TGF-beta signaling through stabilization of SMURF2 by binding to SMURF2 and inhibiting its SMAD7-mediated degradation (By similarity). Involved in glucose homeostasis through induction of glucagon secretion at low glucose levels (By similarity). Promotes dermal fibroblast proliferation and wound repair (PubMed:16472771). Regulates KDELR1-mediated retention of HSP90B1/gp96 in the endoplasmic reticulum (By similarity). Plays a role in angiogenesis by inducing endothelial cell migration at low concentrations and endothelian cell apoptosis at high concentrations (PubMed:12237313). Induces maturation of dendritic cells and monocyte cell adhesion (PubMed:11818442). Modulates endothelial cell responses by degrading HIF-1A through interaction with PSMA7 (PubMed:19362550). {ECO:0000250|UniProtKB:P31230, ECO:0000269|PubMed:10358004, ECO:0000269|PubMed:11157763, ECO:0000269|PubMed:11306575, ECO:0000269|PubMed:11818442, ECO:0000269|PubMed:12237313, ECO:0000269|PubMed:19362550}.
• Disease: DISEASE: Leukodystrophy, hypomyelinating, 3 (HLD3) [MIM:260600]: A severe autosomal recessive hypomyelinating leukodystrophy characterized by early infantile onset of global developmental delay, lack of development, lack of speech acquisition, and peripheral spasticity associated with decreased myelination in the central nervous system. {ECO:0000269|PubMed:21092922}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: tRNA Aminoacylation;Translation;Metabolism of proteins;Metabolism of amino acids and derivatives;Metabolism;Selenoamino acid metabolism;SeMet incorporation into proteins;Cytosolic tRNA aminoacylation (Consensus)

Recessive Scores

• pRec: 0.159

Intolerance Scores

• loftool: 0.976
• rvis_EVS: 0.08
• rvis_percentile_EVS: 60.31

Haploinsufficiency Scores

• pHI: 0.0933
• hipred: Y
• hipred_score: 0.579
• ghis: 0.607

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.477

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Aimp1
• Phenotype: homeostasis/metabolism phenotype; immune system phenotype

Gene ontology

• Biological process: angiogenesis;negative regulation of endothelial cell proliferation;tRNA aminoacylation for protein translation;apoptotic process;chemotaxis;inflammatory response;cell adhesion;signal transduction;cell-cell signaling;response to wounding;regulation of signaling receptor activity;leukocyte migration;defense response to virus;positive regulation of glucagon secretion
• Cellular component: extracellular space;nucleus;endoplasmic reticulum;Golgi apparatus;cytosol;cell surface;membrane;aminoacyl-tRNA synthetase multienzyme complex;methionyl glutamyl tRNA synthetase complex
• Molecular function: tRNA binding;cytokine activity;protein binding;protein homodimerization activity;GTPase binding